Restricted Versus Liberal Fluid Intake for Prevention of Bronchopulmonary Dysplasia (RELIEF)

University Children's Hospital Basel

Status: Begins enrollment in 1 month

Conditions: Bronchopulmonary Dysplasia

Treatments: Other: Fluid restriction; Other: Liberal fluid intake

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT06954142

2025-00321 ks22Schulzke;

Details and patient eligibility

About

The aim of this study is to determine whether restricted fluid intake (135 ±5 mL/kg/day) compared to liberal fluid intake (165 ±5 mL/kg/day) from day 8 of life reduces the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age or prior death in preterm infants born <30 weeks gestational age.

Full description

Complications of preterm birth remain the leading cause of death in children under five years of age worldwide, accounting for approximately one million deaths annually. Among the survivors, bronchopulmonary dysplasia (BPD) is the most common severe complication. BPD is a chronic lung disease characterized by prolonged need for respiratory support and oxygen therapy, poor postnatal growth, and long-term impairments in lung function and neurodevelopment.

Despite advancements in neonatal care, BPD is the most common chronic lung disease in infancy and associated with increased mortality, repeated hospitalisation throughout childhood, impaired lung function up into adulthood, and long-term neurodevelopmental impairment. The incidence of BPD has remained stable over the past 15 years. This is likely due to the improved survival of extremely preterm infants, who are at the highest risk for BPD.

A key feature of evolving BPD is the accumulation of interstitial pulmonary edema, which reduces lung compliance and increases the need for respiratory support, thereby perpetuating a cycle of lung damage.

Currently, diuretics are sometimes used to manage pulmonary edema in preterm infants. While they can improve lung function in the short term, they come with potential risks including bone demineralization, nephrotoxicity, electrolyte imbalances, and impaired growth.

As a potentially safer alternative, fluid restriction is sometimes used to prevent or manage pulmonary edema. It is hypothesized to improve lung mechanics and reduce the need for respiratory support, without the adverse effects associated with medications. However, there is no robust evidence on optimal fluid targets in these patients.

SwissNeoNet, consisting of all nine Swiss NICUs, is a mandatory national registry, where data on all infants born before 32 weeks of gestation and/or with a birth weight < 1501 g are collected. Fluid management practices vary among Swiss neonatal intensive care units (NICUs) following international guidelines recommending 135 to 180 mL/kg/day of fluids. This variation may contribute to the differing rates of BPD and mortality observed across centers, but fluid intake is not routinely captured in SwissNeoNet data, making it difficult to assess its impact.

In summary, although fluid restriction shows potential as a simple and low-risk intervention to reduce the incidence of BPD, current evidence is insufficient to support its routine use. There is a clear need for a robust, contemporary, and pragmatic trial to evaluate whether fluid restriction, started after the first week of life, can safely and effectively reduce the incidence of BPD or death in very preterm infants.

Enrollment: 750 estimated patients

Sex: All

Ages: 8+ days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Hospitalised preterm infants born before 30 weeks 0 days gestation
• Signed informed consent for further research use of health-related data

Exclusion criteria

• congenital malformations
• diseases likely to affect life expectancy, lung function, fluid strategy, or neurodevelopment
• renal disease requiring fluid management outside the clinical standard of care
• congenital heart disease not including patent ductus arteriosus (PDA)

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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750 participants in 2 patient groups

Fluid restriction

Experimental group

Description:

Fluid restriction strategy (fluid target 135 ±5 mL/kg/d)

Treatment:

Other: Fluid restriction

Liberal fluid intake

Active Comparator group

Description:

Liberal fluid intake strategy (fluid target 165 ± 5 mL/kg/d) in line with international best practice recommendations on nutrition.

Treatment:

Other: Liberal fluid intake